Trends in clinical use of targeted therapy for gastrointestinal cancers

Kojiro Eto , Masayuki Watanabe

Journal of Cancer Metastasis and Treatment ›› 2015, Vol. 1 : 163 -71.

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Journal of Cancer Metastasis and Treatment ›› 2015, Vol. 1:163 -71. DOI: 10.4103/2394-4722.166997
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Trends in clinical use of targeted therapy for gastrointestinal cancers

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Abstract

Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal (GI) cancers have recently gained considerable attention. In addition to agents targeting vascular endothelial growth factor (VEGF), epidermal growth factor receptor, the multi-kinase inhibitor, and regorafenib have also become available for the treatment of metastatic colorectal cancer patients. Currently, trastuzumab, an antibody targeting human epidermal growth factor receptor-2 (HER-2), in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive gastric cancer (GC). The efficacy of ramucirumab, a human monoclonal antibody that inhibits VEGF from binding to its receptor in GC, has also been recently demonstrated. At present, a great number of novel targeted drugs are in pre-clinical or clinical studies. In this review, we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating GI cancers, with a focus on emerging strategies for personalized treatment.

Keywords

Gastro-intestinal tumors / molecular pathways / molecular targeted drug

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Kojiro Eto, Masayuki Watanabe. Trends in clinical use of targeted therapy for gastrointestinal cancers. Journal of Cancer Metastasis and Treatment, 2015, 1: 163-71 DOI:10.4103/2394-4722.166997

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References

[1]

Sarmiento R,Gasparini G.Antiangiogenic therapy of colorectal cancer: state of the art, challenges and new approaches..Int J Biol Markers2012;27:e286-94

[2]

Gavalas NG,Trachana SP,Arapinis C,Dimopoulos MA.Angiogenesis-related pathways in the pathogenesis of ovarian cancer..Int J Mol Sci2013;14:15885-909 PMCID:PMC3759892

[3]

Pang RW.Clinical implications of angiogenesis in cancers..Vasc Health Risk Manag2006;2:97-108

[4]

Senger DR,Dvorak AM,Harvey VS.Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid..Science1983;219:983-5

[5]

Shalaby F,Yamaguchi TP,Wu XF,Schuh AC.Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice..Nature1995;376:62-6

[6]

Kawasaki T,Bekku Y,Sanbo M,Fujisawa H.A requirement for neuropilin-1 in embryonic vessel formation..Development1999;126:4895-902

[7]

Fong GH,Gertsenstein M.Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium..Nature1995;376:66-70

[8]

Robinson CJ.The splice variants of vascular endothelial growth factor (VEGF) and their receptors..J Cell Sci2001;114:853-65

[9]

Kleespies A,Jauch KW.Vascular endothelial growth factor in esophageal cancer..J Surg Oncol2004;87:95-104

[10]

Gerber HP,Kowalski J,Keyt BA,Ferrara N.Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation..J Biol Chem1998;273:30336-43

[11]

Robinson KW.EGFR tyrosine kinase inhibitors: difference in efficacy and resistance..Curr Oncol Rep2013;15:396-404

[12]

Mitsudomi T.Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations..Transl Lung Cancer Res2014;3:205-11

[13]

Li Q,Li J.Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas..BMC Cancer2011;11:277 PMCID:PMC3144457

[14]

Witton CJ,Going JJ,Bartlett JM.Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer..J Pathol2003;200:290-7

[15]

Reichelt U,Tsourlakis M,Link BC,Kaifi JT,Yekebas EF,Simon R,Sauter G.Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus..Mod Pathol2007;20:120-9

[16]

Gravalos C.HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target..Ann Oncol2008;19:1523-9

[17]

Tanner M,Junttila TT,Tommola S,Helin H,Joensuu H,Elenius K.Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab..Ann Oncol2005;16:273-8

[18]

Begnami MD,Fregnani JH,Montagnini AL,Soares FA.Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome..J Clin Oncol2011;29:3030-6

[19]

Fakih M.Targeting mechanisms of resistance to anti-EGF receptor therapy in KRAS wild-type colorectal cancer: the path to more personalized medicine..Future Oncol2013;9:551-60

[20]

Bronte G,Rizzo S,Ficorella C,Di Gaudio F,Siragusa S,Russo A.EGFR genomic alterations in cancer: prognostic and predictive values..Front Biosci (Elite Ed)2011;3:879-87

[21]

Engelman JA,Cantley LC.The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism..Nat Rev Genet2006;7:606-19

[22]

Silvestris N,Petriella D,Fistola E,Numico G,Maiello E.The dark side of the moon: the PI3K/PTEN/AKT pathway in colorectal carcinoma..Oncology2009;77 Suppl 1:69-74

[23]

Roberts LR.Hepatocellular carcinoma: molecular pathways and new therapeutic targets..Semin Liver Dis2005;25:212-25

[24]

Avila MA,Sangro B.New therapies for hepatocellular carcinoma..Oncogene2006;25:3866-84

[25]

Kolch W.Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions..Biochem J2000;351(Pt 2):289-305

[26]

Harden TK.Regulation of phospholipase C isozymes by ras superfamily GTPases..Annu Rev Pharmacol Toxicol2006;46:355-79

[27]

To MD,Mao JH.Crosstalk between Pten and Ras signaling pathways in tumor development..Cell Cycle2005;4:1185-8

[28]

Gill S,Sargent DJ,Alberts SR,Benedetti J,Shepherd LE,Labianca R,Cha SS,Goldberg RM.Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much?.J Clin Oncol2004;22:1797-806

[29]

Fearon ER.Molecular genetics of colorectal cancer..Annu Rev Pathol2011;6:479-507

[30]

Gupta A,Mishra AK,Sharma SK.The Wnt pathway: emerging anticancer strategies..Recent Pat Endocr Metab Immune Drug Discov2013;7:138-47

[31]

Martensson A,Jung A,Stenling R.Beta-catenin expression in relation to genetic instability and prognosis in colorectal cancer..Oncol Rep2007;17:447-52

[32]

Wanitsuwan W,Boonpipattanapong T,Sangkhathat S.Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers..World J Gastroenterol2008;14:6052-9 PMCID:PMC2760180

[33]

Elzagheid A,Korkeila E,Syrjanen K.Nuclear beta-catenin expression as a prognostic factor in advanced colorectal carcinoma..World J Gastroenterol2008;14:3866-71 PMCID:PMC2721444

[34]

Okayama H,Harris CC.MicroRNAs and inflammation in the pathogenesis and progression of colon cancer..Dig Dis2012;30 Suppl 2:9-15

[35]

Hagemann T,Lawrence T.Inflammation and cancer: a double-edged sword..Cancer Cell2007;12:300-1 PMCID:PMC2592547

[36]

Greten FR,Greten TF,Li ZW,Kagnoff MF.IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer..Cell2004;118:285-96

[37]

Kojima M,Sasaki N,Mibu R,Katano M.Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression..Anticancer Res2004;24:675-81

[38]

Shiff SJ,Qiao L.Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis..Exp Cell Res1996;222:179-88

[39]

Algra AM.Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials..Lancet Oncol2012;13:518-27

[40]

Flossmann E.Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies..Lancet2007;369:1603-13

[41]

Zhang Y.Epidemiology of esophageal cancer..World J Gastroenterol2013;19:5598-606 PMCID:PMC3769895

[42]

Homs MY,Siersema PD,Kuipers EJ.Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction..Cochrane Database Syst Rev 2006; CD004063

[43]

Mauer AM,Krauss SA,Kasza K,Vokes EE.Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus..Ann Oncol2005;16:1320-5

[44]

Enzinger PC.Esophageal cancer..N Engl J Med2003;349:2241-52

[45]

Lordick F,Chung HC,Oh SC,Kurteva G,Moiseyenko VM,Park JO,Celik I,Melezinkova H.Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial..Lancet Oncol2013;14:490-9

[46]

Waddell T,Cunningham D,Okines AF,Wotherspoon A,Middleton G,Ferry D,Crosby T,Smith D,Iveson T,Slater S,Barbachano Y.Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial..Lancet Oncol2013;14:481-9

[47]

Ling Y,Tao M,Zhang X.A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma..J Thorac Dis2012;4:58-62

[48]

Shah MA,Ilson DH,D'Adamo D,Tse A,Schwartz L,Schwartz GK.Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma..J Clin Oncol2006;24:5201-6

[49]

Shah MA,Ilson DH,Robinson E,Kelsen DP.Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma..J Clin Oncol2011;29:868-74 PMCID:PMC3646322

[50]

Kamangar F,Anderson WF.Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world..J Clin Oncol2006;24:2137-50

[51]

Bang YJ,Feyereislova A,Shen L,Lordick F,Omuro Y,Aprile G,Hill J,Ruschoff J.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial..Lancet2010;376:687-97

[52]

Fuchs CS,Yong CJ,Passalacqua R,Safran H,Aprile G,Melichar B,Topuzov E,Chau I,Sivanandan C,Koshiji M,Liepa AM,Schwartz JD.Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial..Lancet2014;383:31-9

[53]

Wilke H,Van Cutsem E,Bodoky G,Hironaka S,Lipatov O,Cunningham D,Komatsu Y,Emig M,Ferry D,Schwartz JD.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial..Lancet Oncol2014;15:1224-35

[54]

Ohtsu A,Van Cutsem E,Sawaki A,Lim HY,Wu J,Starnawski M.Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study..J Clin Oncol2011;29:3968-76

[55]

Ohtsu A,Bai YX,Chung HC,Sahmoud T,Yeh KH,Muro K,Ferry D,Al-Batran SE,Costantini C,Lebwohl D.Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study..J Clin Oncol2013;31:3935-43

[56]

Janjigian YY,Pauligk C,Kelsen DP,Altmannsberger HM,Tafe LJ,Shah MA.Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis..Ann Oncol2012;23:2656-62

[57]

Spratlin JL,Eadens M,Camidge DR,Leong S,Chow LQ,Meropol NJ,Chiorean EG,Youssoufian H,Eckhardt SG.Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2..J Clin Oncol2010;28:780-7 PMCID:PMC2834394

[58]

Ueda S,Gotoh M,Doi T.A phase ib study of safety and pharmacokinetics of ramucirumab in combination with Paclitaxel in patients with advanced gastric adenocarcinomas..Oncologist2015;20:493-4 PMCID:PMC4425390

[59]

Jemal A,Center MM,Ward E.Global cancer statistics..CA Cancer J Clin2011;61:69-90

[60]

Wieser M,Arnold D,Reinacher-Schick A.Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: a systematic review and meta-analysis of randomized trials..BMC Cancer2010;10:309 PMCID:PMC2908098

[61]

Fearon ER.A genetic model for colorectal tumorigenesis..Cell1990;61:759-67

[62]

Cunningham D,Siena S,Bleiberg H,Bets D,Harstrick A,Chau I.Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer..N Engl J Med2004;351:337-45

[63]

Hurwitz H,Novotny W,Hainsworth J,Berlin J,Griffing S,Ferrara N,Rogers B,Kabbinavar F.Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer..N Engl J Med2004;350:2335-42

[64]

Mayer RJ.Targeted therapy for advanced colorectal cancer-more is not always better..N Engl J Med2009;360:623-5

[65]

Saltz LB,Loehrer PJSr,Kopit J.Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor..J Clin Oncol2004;22:1201-8

[66]

Kim KJ,Winer J,Gillett N,Ferrara N.Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo..Nature1993;362:841-4

[67]

Gerber HP.Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies..Cancer Res2005;65:671-80

[68]

Fuchs CS,Mitchell E,Ganju V,Schulz J,Soufi-Mahjoubi R,Barrueco J.Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study..J Clin Oncol2007;25:4779-86

[69]

Cassidy J,Diaz-Rubio E,Figer A,Koski S,Gilberg F.XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results..Br J Cancer2011;105:58-64 PMCID:PMC3137415

[70]

Hochster HS,Ramanathan RK,Hainsworth JD,Wong L,Abubakr Y,Schwartzberg L.Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study..J Clin Oncol2008;26:3523-9

[71]

Saltz LB,Diaz-Rubio E,Figer A,Koski S,Yang TS,Couture F,Cassidy J.Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study..J Clin Oncol2008;26:2013-9

[72]

Allegra CJ,O'Connell MJ,Petrelli NJ,Atkins JN,Fehrenbacher L,O'Reilly S,Azar CA,Wolmark N.Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08..J Clin Oncol2011;29:11-6 PMCID:PMC3055856

[73]

de Gramont A,Schmoll HJ,Clarke S,Cunningham D,Hecht JR,Im SA,Salazar R,Shacham-Shmueli E,Makrutzki M,Andre T.Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial..Lancet Oncol2012;13:1225-33

[74]

Tabernero J.The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents..Mol Cancer Res2007;5:203-20

[75]

Van Cutsem E,Hitre E,Chang Chien CR,D'Haens G,Lim R,Roh JK,Ruff P,Tejpar S,Nippgen J.Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer..N Engl J Med2009;360:1408-17

[76]

Heinemann V,Decker T,Vehling- Kaiser U,Heintges T,Kahl C,Kullmann F,Scheithauer W,Scholz M,Link H,Rost A,Moehler M,Modest DP,Kirchner T,Stintzing S.FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open- label, phase 3 trial..Lancet Oncol2014;10:1065-75

[77]

Zhang D,Xu T.Treatment related severe and fatal adverse events with cetuximab in colorectal cancer patients: a meta-analysis..J Chemother2013;25:170-5

[78]

Gravalos C,Garcia-Alfonso P.Integration of panitumumab into the treatment of colorectal cancer..Crit Rev Oncol Hematol2010;74:16-26

[79]

Douillard JY,Cassidy J,Burkes R,Humblet Y,Cunningham D,Rivera F,Ruff P,Smakal M,Rother M,Wolf M.Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study..J Clin Oncol2010;28:4697-705

[80]

Douillard JY,Siena S,Burkes R,Humblet Y,Cunningham D,Rivera F,Ruff P,Smakal M,Rother M,Rong A,Sidhu R.Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer..N Engl J Med2013;369:1023-34

[81]

Wilhelm SM,Adnane L,Carter CA,Thierauch KH.Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity..Int J Cancer2011;129:245-55

[82]

Grothey A,Sobrero A,Falcone A,Humblet Y,Mineur L,Adenis A,Yoshino T,Goldberg RM,Cihon F,Wagner A.Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial..Lancet2013;381:303-12

[83]

Chu QS.Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors..Expert Opin Biol Ther2009;9:263-71

[84]

Mitchell EP.Targeted therapy for metastatic colorectal cancer: role of aflibercept..Clin Colorectal Cancer2013;12:73-85

[85]

Van Cutsem E,Lakomy R,Prausova J,Ruff P,Moiseyenko V,McKendrick J,Tellier A,Allegra C.Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen..J Clin Oncol2012;30:3499-506

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